To evaluate the genetic hazard of chemicals in our environment and understand their mode of action it is necessary to use chemical dosimetry of germ cells to place chemical mutagenesis on a quantitative basis. For chemical mutagens that alkylate we determine dosimetry by using radionuclides to measure the alkylations per nucleotide of DNA in germ cells. The genetic effect is measured by detecting metations induced in germ cells of Drosophila melanogaster with an exposure to the nonlabeled alkylating agent equal to the dosimetry exposure. In this project both alkylation and the genetic consequence of alkylation are studied within the same germ cell stage in a eukaryote that can be throughly and economically analyzed genetically. We distinguish between dose, measured as alkylations per nucleotide (AN) of DNA, and exposure of the whole organism, measured as concentration in the feeding solution or the amount injected. The importance of distinguishing between dose and exposure is illustrated in our previous work where we found a non-linear relation between exposure to EMS, concentration in the feeding media, and dose (AN); however, a linear relation was observed between dose and induced mutation frequency. For the dose-response curve no threshold was apparent and the statistical limit of the exponent was 1.0 plus or minus 0.1. The relation between alkylations per nucleotide and mutations suggests that with EMS as the mutagen no change in mechanism of mutagenesis occurs from low to high dose in Drosphilia. Dose-response curves will be determined for other mutagens with different s (Swain-Scott) values and different alkyl groups. Molecular dosimetry of chemical mutagens permits us to distinguish between a non-linear relation of exposure to dose and a linear relation of dose to mutation induction. In comparative mutagenesis it is essential to distinguish between differences among species due to differences in physiology, as would be determined by variations in dose in relation to exposure, and differences due to the mechanism of mutation, as would be detected in variation in the relation of dose to mutagenic effect.